Global occurrence and hazards of benzodiazepines in water resources: Knowledge gaps and future directions

Benzodiazepines (BZDs) are a group of psychoactive pharmaceuticals that are used to treat a variety of medical conditions. Due to the widespread usage of this class of medicines, BZDs have been frequently reported in aquatic systems. We performed a critical review of the refereed literature to better understand the prevalence of BZDs in aquatic matrices and associated water quality hazards. Forty-five BZDs were included in this study, of which 20 compounds have been detected in 5 different aquatic matrices ranging across 6 continents. Most of the aquatic monitoring observations for BZDs were available from Europe, with 1434 maximum measured environmental concentration data points, while 428 and 144 data points were reported from Asia and North America, respectively. Monitoring data gaps were identified in Antarctica, South America, Oceania, and Africa. We identified a temporal change in which BZDs occurrence in sewage, effluents and surface waters increased after initiation of the global COVID-19 pandemic, which appears related to increased prescription rates of these medications to treat mental health conditions. Probabilistic environmental hazard assessments were then performed for compounds with sufficient data using therapeutic hazard values (THVs) and predicted no effect concentrations (PNECs). Over 81 % exceedances of traditional morphometric and behavior PNECs were observed for temazepam and diazepam in African surface waters. Here again, increased exeedances were identified post-COVID-19. Numerous ecotoxicity data gaps were present for almost all BZDs; in fact, sufficient toxicity data to calculate both morphometric and behavioral PNECs was only available for diazepam, oxazepam, and temazepam. Our findings highlight important water quality hazards among global regions and aquatic matrices, which can inform future research efforts to understand and manage BZDs in the environment.